Evaluation of masitinib in the treatment of Progressive Supranuclear Palsy

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2013-003740-23-ES
• Date of registration: 05/12/2013
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: Evaluation of masitinib in the treatment of Progressive Supranuclear Palsy
• Scientific title: A prospective, multicentre, randomised, double-blind, placebo-controlled, parallel groups, phase 2b/3 study to compare the efficacy and safety of masitinib versus placebo in the treatment of patients suffering from Progressive Supranuclear Palsy (PSP)
• Date of first enrolment: 04/02/2015
• Target sample size: 90
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003740-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Spain

Contacts

• Name: Consuelo Pozo
• Affiliation: Alpha Bioresearch, S.L.

• Name: Consuelo Pozo
• Affiliation: Alpha Bioresearch, S.L.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Female or male patient aged between 40 and 80 years old, weighing more than 50 kg and with a Body Mass Index (BMI) between 18 and 35 kg/m².
2. Probable PSP (clinical signs of PSP) with PSP stage ? II defined as:
? at least a 12-month history of postural instability or falls during the first 3 years that symptoms are present; and
? PSPRS score ? 29; and
? an akinetic-rigid syndrome with prominent axial rigidity
3. MAPT H1 positive haplotype
4. Modified Hachinski score ? 3. This modified Hachinski will not include the focal neurological signs, symptoms or pseudobulbar affect questions, given the prominence of all 3 in PSP.
5. Score ? 25 on the mini-mental state examination (MMSE).
6. Patient judged by investigator to be able to comply with neuropsychological evaluation at baseline and throughout the study.
7. Patient must have reliable caregiver accompany him to all study visits. Caregiver and patient must read, understand, and speak local language fluently to ensure comprehension of informed consent form and informant-based assessments of patient. Caregiver must also have frequent contact with patient (at least 3 hours per week at one time or at different times) and be willing to monitor study medication compliance and the patient's health and concomitant medications throughout the study. Patient / caregiver able to understand the patient card and to follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity, during the study.
8. Male or female patient of child bearing potential (entering the study after a menstrual period and who have a negative pregnancy test) must agree to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake
9. Patient residing outside a skilled nursing facility or dementia care facility at the time of screening, and admission to such a facility is not planned. Residence in an assisted living facility is allowed.
10. If the patient is receiving levodopa/carbidopa, levodopa/benserazide, a dopamine agonist, catechol-o-methyltransferase (COMT) inhibitor, or other Parkinson's medication, with the exception of Azilect(rasagiline), the dose must have been stable for at least 60 days prior to the screening visit and must remain stable for the duration of the study. No such medication can be initiated during the study. Subjects receiving rasagiline or CoQ10 must be on a stable dose for at least 90 days prior to the screening visit.
11. Patient able to tolerate the MRI scan during screening with either no sedation or low dose benzodiazepines
12. Patient able to ambulate independently or with assistance defined as the ability to walk at least 30 meters with the assistance of another person who can only have contact with one upper extremity.
13. Patient with life expectancy ? 6 months
14. Patient with adequate organ function at screening and baseline:
? Absolute Neutrophils Count (ANC) ? 2 x 109/L
? Hemoglobin ? 10 g/dL
? Platelets (PTL) ? 100 x 109/L
? AST/ALT ? 2.5 ULN
? Bilirubin
Exclusion criteria:
1. Patient with history of cardiac, hematologic, hepatic, respiratory that is clinically significant for his/her participation in the study
2. Insufficient fluency in local language to complete neuropsychological and functional assessments
3. Diagnosis of Amyotrophic Lateral Sclerosis or other motor neuron disease or other diagnosis of taupathies (such as corticobasal degeneration, frontotemporal lobe dementia, multiple system athrophy)
4. Any of the following condition:
? Abrupt onset of symptoms defined in inclusion criteria 2 associated with ictal events,
? Head trauma related to onset of symptoms defined in inclusion criteria 2,
? Severe amnesia within 6 months of the symptoms defined in inclusion criteria 2,
? Cerebellar ataxia,
? Choreoathetosis,
? Early, symptomatic autonomic dysfunction; or
? Tremor while at rest.
5. Presence of other significant neurological or psychiatric disorders including (but not limited to) Alzheimer's disease; dementia with Lewy bodies; prion disease; Parkinson's disease (which has not subsequently been revised to PSP); any psychotic disorder; severe bipolar disorder; seizure disorder; tumor or other space-occupying lesion; or history of stroke or head injury with loss of consciousness for at least 15 minutes within the past 20 years.
6. Within 4 weeks of screening or during the course of the study, concurrent treatment with memantine; acetylcholinesterase inhibitors; antipsychotic agents (other than quetiapine) or mood stabilizers (e.g., valproate, lithium); treatment with any investigational drugs or device or participation in an investigational drug study within 90 days of screening; or benzodiazepines (except as below):
? Low dose benzodiazepines (not more than 2 mg) may be used for sedation prior to MRI scans for those subjects requiring sedation. Neuropsychological testing may not be performed after benzodiazepines administration.
? Subjects who take short acting benzodiazepines (only temazepam or zolpidem are allowed) for sleep may continue to do so if they have been on a stable dose for 30 days prior to screening.
? Clonazepam may be used for treatment of dystonia or painful rigidity associated with PSP if the dose has been stable for 90 days prior to screening and is not expected to change during the course of the study.
7. Treatment with lithium, methylene blue, tramiprosate, ketone bodies, latrepirdine, or any putative disease-modifying agent directed at tau within 90 days of screening.
8. History of alcohol or substance abuse within 1 year prior to screening and deemed to be clinically significant by the site investigator.
9. History of deep brain stimulator (DBS) surgery.
10. History of early, prominent rapid eye movement (REM) sleep behaviour disorder.
11. Contraindication to MRI examination for any reason (e.g., severe claustrophobia, ferromagnetic metal in body).
12. Structural abnormality on MRI that precludes diagnosis of PSP, such as cortical infarct in brain region that might account for subject's symptoms.
13. Patient with a diagnosis of malignant cancer or evidence of continued disease within five y

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Progressive Supranuclear Palsy
MedDRA version: 14.1 Level: PT Classification code 10036813 Term: Progressive supranuclear palsy System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: masitinib 100mg
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Other descriptive name: MASITINIB MESYLATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: masitinib 200mg
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Other descriptive name: MASITINIB MESYLATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: Assess efficacy of masitinib in the treatment of PSP definied by the evolution of Progressive Supranuclear Palsy Rating Scale (PSPRS) score from week 12 to week 48.

Secondary Objective: Disease progression:
? Brain volume changes, as measured by ventricular volumes, brain stem atrophy and frontal lobe volume
? Serum and cerebrospinal fluid Tau protein levels
Disability level / severity of illness:
? Schwab and England Activities of Daily Living Scale (SEADL) scores from week 12 to week 48
? Clinical Global Impression of Change (CGI-C) scores from week 12 to week 48Clinical Global Impression of Disease Severity (CGI-ds) scores from week 12 to week 48
Cognitive function:
? MMSE scores from week 12 to week 48
? RBANS scores from week 12 to week 48
Psychiatric symptoms:
? Geriatric Depression Scale scores from week 12 to week 48
? Apathy Evaluation Scale scores from week 12 to week 48
Quality of life:
? PSP-QoL scale score from week 12 to week 48
Pharmacokinetics data: Biodisponibility of masitinib at W12 visit, prior to dose increase, compared to W24
Safety: Occurrence of Adverse Events (AE)

Timepoint(s) of evaluation of this end point: from week 12 to week 48

Primary end point(s): Progressive Supranuclear Palsy Rating Scale (PSPRS) score

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Disease progression:
? Brain volume changes week 48.
? Serum and cerebrospinal fluid Tau protein levels week 48.
Disability level / severity of illness:
? Schwab and England Activities of Daily Living Scale (SEADL) scores from week 12 to week 48
? CGI-C scores from week 12 to week 48
CGI-ds scores from week 12 to week 48
Cognitive function:
? MMSE scores from week 12 to week 48
? RBANS scores from week 12 to week 48
Psychiatric symptoms:
? Geriatric Depression Scale scores from week 12 to week 48
? Apathy Evaluation Scale scores from week 12 to week 48
Quality of life:
? PSP-QoL scale score from week 12 to week 48
Pharmacokinetics data:
? Biodisponibility of masitinib at W12 visit, prior to dose increase, compared to W24
Safety:
? Occurrence of Adverse Events

Secondary end point(s): Disease progression:
? Brain volume changes, as measured by ventricular volumes, brain stem atrophy and frontal lobe volume measured by volumetric brain MRI week 48.
? Serum and cerebrospinal fluid Tau protein levels (CSF samples are optional and will be realised only for voluntary patients) week 48.
Disability level / severity of illness:
? Schwab and England Activities of Daily Living Scale (SEADL) scores from week 12 to week 48
? Clinical Global Impression of Change (CGI-C) scores from week 12 to week 48Clinical Global Impression of Disease Severity (CGI-ds) scores from week 12 to week 48
Cognitive function:
? MMSE scores from week 12 to week 48
? RBANS scores from week 12 to week 48

Psychiatric symptoms:
? Geriatric Depression Scale scores from week 12 to week 48
? Apathy Evaluation Scale scores from week 12 to week 48
Quality of life:
? PSP-QoL scale score from week 12 to week 48
Pharmacokinetics data:
? Biodisponibility of masitinib at W12 visit, prior to dose increase, compared to W24
Safety:
? Occurrence of Adverse Events (AE), changes on clinical examination including vital signs (blood pressure, pulse rate) and weight, ECG and laboratory exams (biochemistry, hematology and urinalysis)

Secondary ID(s)

AB13004

Source(s) of Monetary Support

AB Science

Ethics review

Status: Approved
Approval date:
Contact: